This project is designed to study the effects of acute exercise on fuel metabolism, substrate fluxes and oxidation rates in the whole-body and in the exercised and non-exercised limbs, during exercise and in the early (0-4 hours) post-exercise recovery period. Specifically, the role of insulin-deficiency, as found in type I insulin-dependent diabetes mellitus, in altering the rates and patterns of regional fuel delivery and utilization and whole-body metabolism during and after exercise will be examined. Hopefully, these studies will provide new insights into therapeutic maneuvers that will help to normalize these responses in diabetic subjects. Whole body rates of carbohydrate and lipid oxidation and total energy expenditure will be estimated by indirect calorimetry. Total glucose disposal and endogenous glucose production in the basal state and during insulin infusions will be determined by the euglycemic hyperinsulinemic clamp technique combined with D-(3-3H)-glucose infusion. Regional fluxes of substrates (lactate, pyruvate, glucose and amino acids) across non-exercised (forearm) and exercised (leg) limbs will be measured using an "arterialized" hand vein and deep forearm and femoral vein catheters, with forearm blood flow determined non-invasively by impedance plethysmography. Amino acid determinations will be made by HPLC. Whole-body amino acid fluxes and oxidation rates will be determined from stable isotope plasma enrichments using gas chromatography-mass spectrometry (GCMS). This grant will allow me to devote a major effort to continuing and expanding my training in research in diabetes and metabolism, by allowing me to learn and utilize GCMS techniques during a three-month training visit to the Washington University School of Medicine. I view this as an essential part of my career development as an independent clinical investigator. As a member of the University of Vermont Endocrine-Metabolism Unit I will be working with established investigators who will provide their guidance and support in conducting the proposed studies, and will have available the facilities of the Metabolic Unit, Clinical Research Center, and Department of Chemistry which will make it feasible to carry out this research.